Abnormalities found in Alzheimer’s patients’ children

The brains of adults who have elderly parents diagnosed with Alzheimer’s disease betray troubling hallmarks of the same disease even in middle age, when the memory and mental skills of these grown children are still perfectly normal, a new study finds.

Research published Wednesday in the journal Neurology finds that Alzheimer’s-related abnormalities were most pronounced in the brains of those with two parents suffering from the disease.

But among those having just one parent afflicted with Alzheimer’s dementia, less severe abnormalities were evident. Those unusual features followed differing patterns depending whether mother, father or both had been diagnosed. But the findings fell in line with previous research suggesting a person’s risk of developing Alzheimer’s in old age is greater when his or her mother has had the disease than when his or her father has.

None of the 52 subjects, who underwent magnetic resonance imaging, or MRI, scans and two types of PET scans, showed any behavioral signs of suffering from Alzheimer’s. Their ages ranged from 32 to 72, with an average of 56, and all had at least 12 years of education.

The researchers recruited 13 subjects who had a mother diagnosed with the disease after the age of 60, 13 who had a father diagnosed with late-onset Alzheimer’s, and 13 who were unlucky enough to have two parents diagnosed with the memory-robbing disorder.

A final 13 subjects with no family history of Alzheimer’s served as a comparison group. Scattered evenly through all four groups were 19 subjects who were carriers of the APOE-4 genetic variation that confers a higher risk of Alzheimer’s.

Compared with the no-family-history group, the mother-only group and the father-only group, those with two Alzheimer’s-affected parents showed the most reduced overall metabolic activity in their brains and the greatest shrinkage of gray matter in several regions strongly affected in Alzheimer’s disease.

The brains of those with any family history of Alzheimer’s also showed more substantial amyloid plaque deposits than did those without a family history of the disease. But subjects with two parents affected showed the most amyloid plaque – a key hallmark of Alzheimer’s.

Even when the researchers created a smaller group of younger subjects – the 36 who were under 60 – they observed the same patterns of abnormalities. However, the researchers – from New York University School of Medicine and Weill Cornell Medical College – said they could glean no relationship between APOE-4 status and early signs of brain abnormality in the children of Alzheimer’s patients.

While dispiriting news for those who have watched their parents’ minds robbed by Alzheimer’s, the new research may aim at something more hopeful. By detecting and characterizing the earliest signs of Alzheimer’s risk, studies like these may allow physicians to identify those who could benefit from therapies to prevent or delay progression of the disease long before it begins to affect cognitive function.

While no therapy for prevention of Alzheimer’s is yet in hand, researchers and Alzheimer’s activists are putting heavy emphasis on the hunt for an agent or strategy that could nip the disease in the bud, possibly decades before it manifests itself as confusion and memory loss. Chief among them are agents that can disrupt the process of beta-amyloid build-up in the brain, either by improving the brain’s trash removal systems or blocking the chemical process that allows them to form.

In an editorial in JAMA in late December, Dr. Denis A. Evans, a neurologist at Rush University Medical Center, wrote that a shift in emphasis toward Alzheimer’s prevention “seems warranted,” given the swelling numbers of those at risk and the discouraging record of progress in finding therapies to reverse or cure Alzheimer’s.

If they are to identify such a preventive therapy, however, they will need first to identify and track those most at risk – possibly by looking for the earliest changes in brain structure and function that are forerunners to dementia symptoms.